Cardiac Resynchronisation Therapy (CRT) has an established role in the treatment of patients with severe left ventricular systolic dysfunction (LVED) and symptomatic heart failure despite optimal medical therapy (OMT).1,2 The aim of CRT is to restore a physiological contraction pattern to the ventricles in patients with mechanical dyssynchrony.3 The landmark COMPANION and CARE-HF studies concluded that de novo CRT implantation is associated with decreased all-cause mortality.4,5 CRT has also been shown to lead to an improvement in patient symptoms, a reduction in hospitalisation, and increased survival.2 Recommendations for CRT implantation are now engrained in national and international guidelines.6,7

What is less well understood are the indications and selection criteria for upgrading conventional bradyarrhythmia pacemakers or implantable cardioverter defibrillator devices (ICDs) to CRT devices as this population have largely been excluded from conventional trials.8 Right ventricular (RV) pacing, usually via an endocardial pacing system, is the standard treatment of patients with bradyarrhythmias.3 The depolarisation of the interventricular septum from right to left is the opposite of normal physiological septal depolarisation.9 Indeed, a left bundle branch block pattern on the 12-lead electrocardiogram is one method of confirming correct positioning of the right ventricular lead. This abnormal electrical depolarisation leads to abnormal mechanical contraction with both intra- and interventricular dyssynchrony.10 This in turn may precipitate left ventricular remodelling (myofibrillar disarray and asymmetrical septal hypertrophy) and lead to the development of heart failure symptoms or worsening of pre-existing heart failure. Heart failure related hospitalisation and death has been directly related to cumulative percentage of RV pacing.1,10 One cross sectional study identified heart failure in as many as 27% of patients attending a typical pacing clinic.1 Randomised studies comparing right atrial and right ventricular pacing implicate RV pacing as the aetiology of heart failure in up to 40% of implanted individuals programmed to VVIR mode.3

A number of studies have investigated the outcomes of patients upgraded from bradyarryhthmia pacing or ICD to CRT. The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) group performed a sub analysis comparing patients implanted de novo with CRT devices against those who were upgraded to CRT-D and identified a 90% response rate in the upgrade group.2 A separate study recruited 112 patients who had a left ventricular ejection fraction (LVEF) of ≤35% and chronic right ventricular pacing (>85% or atrioventricular node ablation).8 64.3% met the criteria for being a responder (defined as ≥15% reduction in left ventricular end systolic volume - LVESV). Responders had a significantly greater reduction in QRS duration (-26.4 ± 33.2ms vs -11.1 ± 39.8ms in de novo implants). Sideris et al compared patients pre and post upgrade to CRT-P or CRT-D from RV pacing, with NHYA class III to IV symptoms despite OMT.3 Improvement in symptoms was seen in >85% (reduction in NYHA score by ≥1) with improved 6-minute walk tests and reduced hospitalisations. LVEF was increased by an average from 26.3 ± 5.4% to 31.4 ± 6.7%. Foley et al studied patients in NYHA class III/IV heart failure with LVEF ≤35%, a QRS duration of ≥120ms and on optimal medical therapy.1 81% were RV pacing at the time of the procedure. Patients were only included if upgraded to CRT-P as per the CARE-HF study.5 There were no differences in the response rates or complications. The upgraded group showed evidence of reverse remodelling (reduced LV end systolic volume -LVESV).

Unique from other investigators, van Geldorp et al recruited patients who did not need to have heart failure symptoms.9 The 37 patients enrolled were required to have >95% RV pacing, a left ventricular end diastolic dimension (LVEDD) >55mm, or LVEF <40% despite optimal medical therapyand optimal pacing settings. There was a six-month crossover design with patients blinded to whether they were RV or bi-ventricular paced. Patients significantly preferred biventricular pacing. LVEF increased by an average of 7%, there was a reduction in LVEDD of 4%, and significant improvements in NYHA class. In a sub-analysis of patients in NYHA class I/II the treatment effects were similar to those seen in the entire treatment group with reduction in LVESV of 15%.

The European CRT survey provides an overview of practices in 13 European countries.10 In keeping with other published data, patients undergoing device upgrades tend to be older men. The native QRS duration is greater than in individuals undergoing de novo implants. Of all CRT devices implanted about one quarter are upgrades.

Guidelines now include advice on when to consider upgrading bradyarrhythmia and ICD devices to CRT. The European Society of Cardiology (ESC) recommend considering CRT in patients requiring permanent or frequent RV pacing for bradycardia who have symptomatic heart failure or reduced LVEF.7 The guideline development group point to evidence of subjective improvement, less hospitalisation and improved cardiac function when upgrading is sufficient to permit a general consensus of opinion in favour of upgrading. Evidence that CRT is indicated (upgrade from conventional PM to CRT) in HF patients with LVEF <35% and high percentage of ventricular pacing who remain symptomatic despite adequate medical treatment is given a class I B status. The EHA/HRA guidelines reflect this general consensus with the caveat that the operator should be well trained in the procedure.6

Yet the practice of upgrading from bradyarrhythmia pacing systems or ICD is not generally widespread.3 Some implanters may be deterred from performing upgrade procedures by data suggesting an increase in complications when compared to de novo implants. Increased risk of infection, venous access issues, and damage to existing leads are all concerns that have been raised in relation to upgrades.11 General consensus, supported by ‘real life’ data purports an increased risk with any re-intervention.12 A prospect data collection study investigated patients undergoing pacemaker generator updates versus those undergoing additional lead implant (n=713).13 They identified 0.7% with a peri-procedural complication (pneumothorax, cardiac perforation, cardiac arrest), 2.5% requiring prolonged hospital admission for the treatment of heart failure symptoms, and 1.5% requiring a haematoma evacuation. There were eight procedure related deaths within 30 days. However, this group were not comparing upgrades with de novo complications, out of keeping with other studies. There were no differences in rate of infection. A retrospective comparison of 134 upgrade patients (with LVEF ≤35%, NHYA III/IV and high percentage of RV pacing) with an equal number of randomly selected de novo implants identified complications including phrenic nerve stimulation, coronary sinus dissection, and pocket haematoma.14 There were no significant differences in early complications. Of the 8% of patients who had subclavian vein thrombosis, all were able to be circumvented. However, the implanters in this cohort may not be typical due to their extensive experience in the field. The European survey showed no difference in complications or outcomes between de novo and upgraded individuals.10

In light of the evidence presented here, a number of questions arise. Namely (i) should asymptomatic patients with a high percentage of right ventricular pacing be screened for possible device upgrade?15 (ii) when is the optimal time to perform an upgrade procedure? and (iii) should patients be clinically evaluated before routine box change, including assessment of left ventricular parameters? An increased awareness of the problem is the beginning but more evidence is needed to address the question of who should be interested in an upgrade.